fac-[Re(CO)3(H2O)3]+ nucleoside monophosphate adducts investigated in aqueous solution by multinuclear NMR spectroscopy

The fac-[Re(CO)3(H2O)3]+ cation, the putative DNA-binding species accounting for the biological activity of related Re(I) complexes, binds reversibly to N7 of 6-oxopurine nucleotide monophosphates (NMPs), in contrast to Pt(II) anticancer drugs. A relatively high amount of NMP is needed to convert all of the fac-[Re(CO)3(H2O)3]+ to adducts. The Re/nucleotide 1:1 adduct forms more rapidly and builds up to a higher concentration for guanosine 5'-monophosphate (5'-GMP) and inosine 5'-monophosphate (5'-IMP) than for the respective 3'-monophosphates (3'-GMP and 3'-IMP). These results are attributable to the 5'-positioning of the 5'-NMP phosphate group that allows it to approach the metal inner sphere for more favorable cation electrostatic and aqua ligand H-bonding interactions, both in the initial productive ion pair encounter complexes and in the N7-bound 1:1 adducts. A higher reactivity of 5'-GMP over 3'-GMP is known for cisplatin. In contrast, more Re/nucleotide 1:2 adduct was formed by 3'-GMP (and 3'-IMP) than by 5'-GMP (and 5'-IMP). Because the 3'-phosphate group cannot closely approach the metal inner coordination sphere, the greater stability for the 3'-GMP 1:2 adduct reflects the more favorable G N1H-phosphate interligand GMP-GMP interactions for 3'-GMP vs 5'-GMP (G=guanine base derivative). This type of interaction is known for platinum adducts. In 1:2 adducts the bound nucleotides are inequivalent, prompting us to perform mixed 5'-GMP/3'-GMP experiments, leading to the observation of major (M) and minor (m) mixed Re/5'-GMP/3'-GMP 1:1:1 adducts. The order of abundance at equilibrium in a typical experiment was M>bis 3'-GMP>m>or=bis 5'-GMP. This stability order was rationalized by invoking the phosphate interactions described above. When methionine and 5'-GMP were allowed to compete for fac-[Re(CO)3(H2O)3]+, the Re/5'-GMP 1:1 adduct was the kinetic product and the S-bound Re/methionine adduct was the thermodynamic product, a result opposite to that typically found for cisplatin.     

Characterization and application of the fac-[188Re(CO)3(H2O)3]+ core

Summary Fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ was synthesized with an overall radiochemical yield of 80±5%, and more than 95% radiochemical purity after a QMA Sep-Pak column separation. Fac-[Re(CO)₃(H₂O)₃]⁺ was also synthesized as a reference sample. The structure of the precursor, fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺, was confirmed by high performance of liquid chromatography (HPLC). MN-His (magnetic nanoparticles coated with silica and modified with an amino silane coupling agent, N-[3-(trimethyoxysilyl)propyl]-ethylenediamine (SG-Si900) and immobilized with histidine) was labeled with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ and an initial animal test of MN-His was conducted for a magnetic targeting study.     

Mechanistic changeover for the water substitution on fac-[(CO)3Re(H2O)3]+ revealed by high-pressure NMR

The complex formation in water between the stable tricarbonyltriaqua fac-[(CO)(3)Re(H(2)O)(3)](+) (1) complex and N- and S-donor ligands has been studied by high-pressure (1)H NMR. Rate and equilibrium constants for the formation of [(CO)(3)Re(Pyz)(H(2)O)(2)](+), [(CO)(3)(H(2)O)(2)Re(mu-Pyz)Re(H(2)O)(2)(CO)(3)](2+), [(CO)(3)Re(THT)(H(2)O)(2)](+), and [(CO)(3)Re(DMS)(n)()(H(2)O)(3-n)](+) (n = 1-3) (Pyz = pyrazine, THT = tetrahydrothiophene, DMS = dimethyl sulfide) have been determined and are in accord with previous results (Salignac, B.; Grundler, P. V.; Cayemittes, S.; Frey, U.; Scopelliti, R.; Merbach, A. E.; Hedinger, R.; Hegetschweiler, K.; Alberto, R.; Prinz, U.; Raabe, G.; K?lle, U.; Hall, S. Inorg. Chem. 2003, 42, 3516). The calculated interchange rate constant k(1)' (Eigen-Wilkins mechanism) increases from the hard O- and N-donors to the soft S-donors, as exemplified by the following series: TFA (trifluoroacetate) (k(1)' = 2.9 x 10(-3) s(-1)) < Br(-) < CH(3)CN < Pyz < THT < DMS < TU (thiourea) (k(1)' = 41.5 x 10(-3) s(-1)). On the other hand, values remain close to that of water exchange k(ex) on 1 (k(ex) = 6.3 x 10(-3) s(-1)). Thus, an I(d) mechanism was assigned, suggesting however the possibility of a slight deviation toward an associatively activated mechanism with the S-donor ligands. Activation volumes determined by high-pressure NMR, for Pyz as Delta V(++)(f,1) = +5.4 +/- 1.5, Delta V(++)(r,1) = +7.9 +/- 1.2 cm(3) mol(-)(1), for THT as Delta V(++)(f,1) = -6.6 +/- 1, Delta V(++)(r,1) = -6.2 +/- 1 cm(3) mol(-1), and for DMS as Delta V(++)(f,1) = -12 +/- 1, Delta V(++)(r,1) = -10 +/- 2 cm(3) mol(-1) revealed the ambivalent character of 1 toward water substitution. Hence, these findings are interpreted as a gradual changeover of the reaction mechanism from a dissociatively activated one (I(d)), with the hard O- and N-donor ligands, to an associatively activated one (I(a)), with the soft S-donor ligands.     

Post-protein-binding reactivity and modifications of the fac-[Re(CO)3]+ core

The reactivity of the [Re(CO)(3)(H(2)O)(2)](+) complex coordinated to the His15 residue of HEW lysozyme is described. In the fully metalated protein (Lys-1), the Re ion retains its reactivity only toward selected ligands, while others induce a ligand-mediated demetalation of the enzyme. It is further shown that some of the complexes that may be "engineered" on the lysozyme do not react with the free protein even if present in solution in excess. The formation of stable metal adducts starting from Lys-1 was confirmed by X-ray crystallography.     

The chemistry of the fac-[Re(CO)2(NO)]2+ fragment in aqueous solution

The anions [ReX3(CO)2(NO)]- (with X = Cl, 1; X = Br, 2) have been prepared with different counterions. Complex 1 was found to lose its chloride ligands in water within 24 h. The [Re(H2O)3(CO)2(NO)]2+ cation obtained after hydrolysis is a strong acid, which consequently undergoes a slow condensation reaction in water to form the very stable [Re(mu3-O)(CO)2(NO)]4 cluster 4 at pH > 2, that precipitates from the aqueous solution and is insoluble also in organic solvents. Fast deprotonation of [Re(H2O)3(CO)2(NO)]2+ did not lead to 4 but rather to the mononuclear species [Re(OH)(H2O)2(CO)2(NO)]+. Subsequent attack of OH- at a CO group resulted in the formation of a rhenacarboxylic acid and its carboxylate anion. For solutions of even higher pH, IR spectroscopy provided evidence for the formation of a Re(C(O)ON(O)) species. These processes were found to be reversible on lowering the pH. Starting from cluster 4 it was possible to obtain complexes of the types [ReX(CO)2(NO)L2] or [Re(CO)2(NO)L3](L2 = 2-picolinate, 2,2'-bipyridine, L-phenylalanate; L3 = tris(pyrazolyl)methane, 1,4,7-trithiacyclononane) in the presence of an acid in protic solvents, but only in low yields. In further synthetic studies, complexes 1 and 2 were found to be superior starting materials for substitution reactions to form [ReX(CO)2(NO)L2] or [Re(CO)2(NO)L3] complexes.     

Binding interaction of [Re(H2O)3(CO)3]+ with the DNA fragment d(CpGpG)

Insights into the interaction of the [Re(H2O)3(CO)3]+ complex (1) with the DNA fragment d(CpGpG) have been obtained by one- (1D) and two-dimensional (2D) NMR spectroscopy. The H8 resonances of the single major [Re(H2O)d(CpGpG)(CO)3]- adduct (2) exhibit pH-independent chemical shift changes attributable to metal N7 binding. The structure of this adduct has been characterized by molecular modeling studies based on 1D and 2D NMR data. In solution, 2 shows the presence of two N7-coordinated guanine moieties in a head-to-head (HH) orientation as evidenced by G2H8/G3H8 cross-peaks in the 1H-1H NOESY NMR spectrum. The presence of the 5'-bridging phosphodiester appears to stabilize the HH1 L conformer, as was previously described for related Pt and Rh complexes.     

Reactions of the Re(CO)3(H2O)3(+) synthon with monodentate ligands under aqueous conditions

The reactions of ammonia, pyridine (py), N-methyl imidazole (N-MeIm), tetrahydrothiophene (tht), and piperidine (pip) with Re(CO) 3(H 2O) 3 (+), 1 ( + ), were investigated employing aqueous conditions under atmospheric dioxygen. The reaction of [ 1]Br in aqueous ammonia led to [Re(CO) 3(NH 3) 3]Br ([ 2]Br) as the only product isolated. For the aqueous reactions of [ 1]Br with py, N-MeIm, and tht, mixtures of products are formed because of competition between the bromide and added ligand, even when the ligand is present in excess. Substitution of the PF 6 (-) anion for Br (-) leads to the clean formation of [Re(CO) 3L 3][PF 6] ([ 3][PF 6]-[ 5][PF 6]) for py, N-MeIm, and tht, respectively, as the only products observed. Reaction of [ 1][PF 6] with pip produces the dimeric species, (pip)(CO) 3Re(micro-OH) 2Re(CO) 3(pip), 6. Reactions of [ 1]Br were also performed in methanol for comparison purposes. The reaction with pip in this solvent led to the analogous dimer, (pip)(CO) 3Re(micro-OMe) 2Re(CO) 3(pip), 7; however, reactions with py, N-MeIm, and tht gave Re(CO) 3L 2Br, 8- 10, respectively, as the only products. The crystal structures of compounds [ 2]Br- 10 are reported.     

The organometallic fac-[(CO)3Mn(H2O)3]+ aquaion: base-hydrolysis and kinetics of H2O-substitution

The novel organometallic aqua complex [(CO)(3)Mn(H(2)O)(3)](+) (1(+)) was obtained through hydrolysis of the analogous acetone complex. IR [nu(CO) = 2051, 1944 cm(-)(1)] and (17)O NMR spectroscopy revealed the presence of a fac tricarbonyl unit. Potentiometric titrations established that the trimer [(CO)(3)Mn(3)(OH)(4)](-) was the principal condensation product in the pH range >6 prior to slow formation of the tetramer [[(CO)(3)Mn](OH)](4). Water exchange in 1(+), determined by NMR line broadening as k(ex) = 19 +/- 4 s(-)(1) at 298 K, is four orders faster than with the analogous Re complex. The activation volume DeltaV(++) = -4.5 +/- 0.4 cm(3) mol(-1) is indicative of an associatively activated (I(a)) process.     

fac-[Re(CO)3(dmso-O)3](CF3SO3): a new versatile and efficient Re(I) precursor for the preparation of mono and polynuclear compounds containing fac-[Re(CO)3]+ fragments

We show here that the new complex fac-[Re(CO)3(dmso-O)3](CF3SO3) (1), efficiently prepared in one step from [ReBr(CO)5] and featuring a broad range of solubility, is, in general, a better precursor for the one-step synthesis of mono- and polynuclear inorganic compounds containing fac-[Re(CO)3]+ fragments compared to the commonly used (NEt4)2fac-[ReBr3(CO)3] and fac-[Re(CO)3(CH3CN)3](Y) (Y = PF6, BF4, ClO4) species. Compound 1 is the first example of a Re(I)-dmso complex structurally characterized and confirms the rule that dmso is always O-bonded when trans to CO. The reactivity of 1 was tested in the one-step preparation of several new and known complexes. The O-bonded sulfoxides of 1 are replaced under mild conditions by tri- (L3) and bidentate ligands (L2) to produce fac-[Re(CO)3(L3)]+ and fac-[Re(CO)3(L2)(dmso-O)]+ compounds, respectively. An excess of monodentate ligands (L) and more forcing conditions are needed to prepare fac-[Re(CO)3(L)3]+ compounds. The new compounds include fac-[Re(CO)3(bipy)(dmso-O)](CF3SO3) (4), that turned out to be an excellent precursor for binding the luminescent fac-[Re(CO)3(bipy)]+ fragment to polytopic ligands for the construction of more elaborate assemblies. One example reported here is the two-step preparation of fac-[{Re(CO)3(bipy)}(mu-4,4'-bipy){Ru(TPP)(CO)}](CF3SO3) (8) (TPP = tetraphenylporphyrin). The X-ray structures of the new compounds 1, 4, of the bis-porphyrin complex fac-[Re(CO)3Cl(4'MPyP)2] (13) (4'MPyP = 5-(4'pyridyl)-10,15,20-triphenylporphyrin), and of the rhenium-cyclophane [{(CO)3Re(mu-OH)2Re(CO)3}2(micro-4,4'-bipy)2] (15), among others, are described. Compound 1 might find useful applications in supramolecular chemistry (metal-mediated assembly of large architectures), in the in situ preparation of stable Re compounds to be used in nuclear medicine, and for the labeling of biomolecules.     

Reactivity of the organometallic fac-[(CO)3ReI(H2O)3]+ aquaion. Kinetic and thermodynamic properties of H2O substitution

The water exchange process on [(CO)(3)Re(H(2)O)(3)](+) (1) was kinetically investigated by (17)O NMR. The acidity dependence of the observed rate constant k(obs) was analyzed with a two pathways model in which k(ex) (k(ex)(298) = (6.3 +/- 0.1) x 10(-3) s(-1)) and k(OH) (k(OH)(298)= 27 +/- 1 s(-1)) denote the water exchange rate constants on 1 and on the monohydroxo species [(CO)(3)Re(I)(H(2)O)(2)(OH)], respectively. The kinetic contribution of the basic form was proved to be significant only at [H(+)] < 3 x 10(-3) M. Above this limiting [H(+)] concentration, kinetic investigations can be unambiguously conducted on the triaqua cation (1). The variable temperature study has led to the determination of the activation parameters Delta H(++)(ex) = 90 +/- 3 kJ mol(-1), Delta S(++)(ex) = +14 +/- 10 J K(-1) mol(-1), the latter being indicative of a dissociative activation mode for the water exchange process. To support this assumption, water substitution reaction on 1 has been followed by (17)O/(1)H/(13)C/(19)F NMR with ligands of various nucleophilicities (TFA, Br(-), CH(3)CN, Hbipy(+), Hphen(+), DMS, TU). With unidentate ligands, except Br(-), the mono-, bi-, and tricomplexes were formed by water substitution. With bidentate ligands, bipy and phen, the chelate complexes [(CO)(3)Re(H(2)O)(bipy)]CF(3)SO(3) (2) and [(CO)(3)Re(H(2)O)(phen)](NO(3))(0.5)(CF(3)SO(3))(0.5).H(2)O (3) were isolated and X-ray characterized. For each ligand, the calculated interchange rate constants k'(i) (2.9 x 10(-3) (TFA) < k'(I) < 41.5 x 10(-3) (TU) s(-1)) were found in the same order as the water exchange rate constant k(ex), the S-donor ligands being slightly more reactive. This result is indicative of I(d) mechanism for water exchange and complex formation, since larger variations of k'(i) are expected for an associatively activated mechanism.     

Kristallstruktur von (NMe4)2[Re3Br11(H2O)] [Re3Br9(H2O)3](H2O)2

Crystal Structure of (NMe₄)₂[Re₃Br₁₁(H₂O)] [Re₃Br₉(H₂O)₃](H₂O)₂ . (NMe₄)₂[Re₃Br₁₁(H₂O)] [Re₃Br₉(H₂O)₃](H₂O)₂ crystallizes from hydrobromic acid solution of Re₃Br₉ · 2 H₂O and NMe₄Br at 0 – 5°C. The crystal structure (monoclinic; P2₁/m (Nr. 11); a = 967.9(3); b = 1 529.7(4); c = 1 710.9(4) pm; β = 91.66(2)°; Z = 2; R = 0.113; R_w = 0.068) has been determined from four-circle diffractometer data. The structure contains two different cluster units of trivalent rhenium, isolated anionic [Re₃Br₁₁(H₂O)]^2? units and neutral cluster units that are connected through crystal water molecules to chains{[Re₃Br₉(H₂O)₃](H₂O)₂}.     

Iron oxide-filled micelles as ligands for fac-[M(CO)3]+ (M = (99m)Tc, Re)

Magnetite-filled micelles capture fac-[M(OH(2))(3)(CO)(3)](+) complexes (M = (99m)Tc, Re), creating versatile self-assembled constructs for multimodal SPECT/MR/optical imaging and radiopharmaceutical guided delivery.     

Formation of a six-coordinate fac-[Re(CO)3]+ complex by the N-C bond cleavage of a potentially tetradentate ligand

The rhenium(I) compound fac-[Re(CO)₃(daa)].Hpab.H₂O (Hpab = N,N’-(1,2-phenylene)bis(2′-aminobenzamide); Hdaa = 2- amino-N-(2-aminophenyl)benzamide) was synthesized from the reaction of [Re(CO)₅Br] with two equivalent of Hpab in toluene. The monoanionic tridentate ligand daa was formed by the rhenium-mediated cleavage of an amido N-C bond of the potentially tetradentate ligand Hpab. The compound was characterized by IR spectroscopy and X-ray crystallography, and daa is coordinated as a diaminoamide via three nitrogen-donor atoms.     

Synthesis of 17-alpha-substituted estradiol-pyridin-2-yl hydrazine conjugates as effective ligands for labeling with Alberto's complex fac-[Re(OH2)3(CO)3]+ in water

The development of (99m)Tc-estradiol radiopharmaceuticals would be advantageous for the detection of estrogen receptor-positive breast tumors. Estradiol derivatives conjugated to organometallic tricarbonyl-Tc(I) and related Re(I) complexes are capable of achieving high receptor binding affinity, but effective methods for synthesizing radiolabeled complexes in water are not available. Our interest in the synthesis of 2-hydrazinopyridines as ligands for Tc and Re led us to investigate Pd-catalyzed amination reactions of halo-pyridine substrates with di-tert-butyl hydrazodiformate. Both 2- and 4-substituted halo-pyridine substrates undergo C-N coupling with di-tert-butyl hydrazodiformate to produce Boc-protected pyridine hydrazine derivatives. Only highly electrophilic 3-pyridine halides were converted to the hydrazine. The Boc-protected 5-bromopyridin-2-yl hydrazine substrate 3 was prepared by regioselective substitution at the 2-position of 2,5-dibromopyridine. This bifunctional chelate was attached to ethynyl or vinyl groups at the 17alpha position of estradiol, using Sonogashira and Suzuki/Miyaura coupling reactions to synthesize 1 and 2 in high yields, respectively. Deprotection of 1 under acidic conditions provided the hydrazine hydrochloride salt 25. The 17alpha-estradiol-tricarbonylrhenium(I) complex 4 was synthesized by labeling 25 with fac-[Re(OH(2))(3)(CO)(3)](+) in aqueous ethanol. This complex exhibited excellent stability and high receptor binding affinity for the estrogen receptor, and it is a promising model for evaluation of the analogous Tc-99m complexes as diagnostic imaging agents for breast tumors.     

Why [CpW(CO)3]+ reduces H2 to dihydride

The [CpW(CO)3]+ complex, with three pi acceptor ligands and a positive charge, is shown to have an unexpected reducing ability towards H2 because of a low lying triplet state energy.     

Relevance of the ligand exchange rate and mechanism of fac-[(CO)3M(H2O)3]+ (M = Mn, Tc, Re) complexes for new radiopharmaceuticals

The water exchange process on fac-[(CO)3Mn(H2O)3]+ and fac-[(CO)3Tc(H2O)3]+ was kinetically investigated by 17O NMR as a function of the acidity, temperature, and pressure. Up to pH 6.3 and 4.4, respectively, the exchange rate is not affected by the acidity, thus demonstrating that the contribution of the monohydroxo species fac-[(CO)3M(OH)(H2O)2] is not significant, which correlates well with a higher pKa for these complexes compared to the homologue fac-[(CO)3Re(H2O)3]+ complex. The water exchange rate K298ex/s(-1) (DeltaHex double dagger/kJ mol(-1); DeltaSex double dagger/J mol(-1) K(-1); DeltaV double dagger/cm3 mol-1) decreases down group 7 from Mn to Tc and Re: 23 (72.5; +24.4; +7.1) > 0.49 (78.3; +11.7; +3.8) > 5.4 x 10(-3) (90.3; +14.5; -). For the Mn complex only, an O exchange on the carbonyl ligand could be measured (K338co = 4.3 x 10(-6) s(-1)), which is several orders of magnitude slower than the water exchange. In the case of the Tc complex, the coupling between 17O (I = 5/2) and 99Tc (I = 9/2) nuclear spins has been observed (1J99Tc,17O = 80 +/- 5 Hz). The substitution of water in fac-[(CO)3M(H2O)3]+ by dimethyl sulfide (DMS) is slightly faster than that by CH3CN: 3 times faster for Mn, 1.5 times faster for Tc, and 1.2 times faster for Re. The pressure dependence behavior is different for Mn and Re. For Mn, the change in volume to reach the transition state is always clearly positive (water exchange, CH3CN, DMS), indicating an Id mechanism. In the case of Re, an Id/Ia changeover is assigned on the basis of reaction profiles with a strong volume maximum for pyrazine and a minimum for DMS as the entering ligand.     

Ultrafast excited-state dynamics preceding a ligand trans-cis isomerization of fac-[Re(Cl)(CO)3(t-4-styrylpyridine)2] and fac-[Re(t-4-styrylpyridine)(CO)3(2,2'-bipyridine)]+

UV-vis absorption and resonance Raman spectra of the complexes fac-[Re(Cl)(CO)3(stpy)2] and fac-[Re(stpy)(CO)3(bpy)]+ (stpy = t-4-styrylpyridine, bpy = 2,2'-bipyridine) show that their lowest absorption bands are dominated by stpy-localized intraligand (IL) pi pi* transitions. For the latter complex a Re --> bpy transition contributes to the low-energy part of the absorption band. Optical population of the 1IL excited state of fac-[Re(Cl)(CO)3(stpy)2] is followed by an intersystem crossing (< or =0.9 ps) to an 3IL state with the original planar trans geometry of the stpy ligand. This state undergoes a approximately 90 degrees rotation around the stpy C=C bond with a 11 ps time constant. An electronically excited species with an approximately perpendicular orientation of the phenyl and pyridine rings of the stpy ligand is formed. Conversion to the ground state and isomerization occurs in the nanosecond range. Intraligand excited states of fac-[Re(stpy)(CO)3(bpy)]+ show the same behavior. Moreover, it was found that the planar reactive 3IL excited state is rapidly and efficiently populated after optical excitation into the Re --> bpy 1MLCT excited state. A 1MLCT --> 3MLCT intersystem crossing takes place first with a time constant of 0.23 ps followed by an intramolecular energy transfer from the ReI(CO)3(bpy) chromophore to a stpy-localized 3IL state with a 3.5 ps time constant. The fast rate ensures complete conversion. Coordination of the stpy ligand to the ReI center thus switches the ligand trans-cis isomerization mechanism from singlet to triplet (intramolecular sensitization) and, in the case of fac-[Re(stpy)(CO)3(bpy)]+, opens an indirect pathway for population of the reactive 3IL excited state via MLCT states.     

Re(CO)(3) complexes synthesized via an improved preparation of aqueous fac-[Re(CO)(3)(H(2)O)(3)](+) as an aid in assessing (99m)Tc imaging agents. Structural characterization and solution behavior of complexes with thioether-bearing amino acids as tridentate ligands

Parallel studies of the preparation of Re and (99m)Tc agents aid in interpreting the nature of tracer (99m)Tc radiopharmaceuticals. Aqueous solutions of the fac-[(99m)Tc(CO)(3)(H(2)O)(3)](+) cation are gaining wide use and are readily prepared, but such solutions of the fac-[Re(CO)(3)(H(2)O)(3)](+) cation (1) are not so easily accessible. Herein we describe a new, reliable, and straightforward preparation of aqueous solutions of 1, characterized by HPLC and ESI-MS. Treatment of solutions of 1 with thioether-bearing amino acids, AAH = S-methyl-l-cysteine (MECYSH), S-propyl-l-cysteine (PRCYSH), and methionine (METH), gave high yields of fac-Re(CO)(3)AA complexes. X-ray crystallographic and NMR analyses indicated that MECYS(-), PRCYS(-), and MET(-) were bound in fac-Re(CO)(3)AA complexes as tridentate monoanionic ligands through amino, thioether, and alpha-carboxyl groups. In CD(3)OD, (1)H NMR spectra have broad signals but have two sets of signals at -10 degrees C, consistent with two isomers with different configurations at the pyramidal sulfur; these interconvert slowly on the NMR time scale at low temperatures. Indeed, the crystal structure of the fac-Re(CO)(3)(PRCYS) reveals a mixture of the two possible diastereoisomers. S-(Carboxymethyl)-l-cysteine (CCMH(2)) and 1 gave two products, 5A (kinetically favored) and 5B (thermodynamically favored). X-ray crystallographic analyses of a crystal of 5B and of a 1:1 cocrystal of 5A and 5B showed that 5A and 5B are diastereoisomers with the CCMH(-) alpha-carboxyl group dangling. In addition to the amino and thioether groups, the S-(carboxymethyl) carboxyl group is coordinated, a feature that slows interconversion of diastereoisomers relative to the other fac-Re(CO)(3)AA complexes because interconversion can now occur only after the rupture of Re-ligand bonds. These N, O, and S tridentate adducts are quite stable, and the grouping has promise in (99m)Tc(CO)(3) tracer development.     

Diazenide and hydrazide(2-) derivatives of the [Re(CO)3]+ core

Reaction of [ReBr3(CO)3]2- with aryldiazonium salts gives the Re(iii) diazenide complexes [ReBr2(NNC6H4R-4)(CO)2]-. The attachment of a PhNHCS tethering group to pyridyl hydrazine generates a HYNIC related proligand which gives a stable chelated pyridyliumthiocarbazide(2-) derivative of the [Re(I)(CO)3]+ core.